Synthesis of vitamin E and quinone intermediates

ABSTRACT

A synthesis of Vitamin E has the condensation of 2,4-pentanediene and 1,2-epoxy-2,6,10,14-tetramethylpentadecane including intermediates in this synthesis which uses base catalyzed condensations of aliphatic compounds to construct the Vitamin E molecule from aliphatic precursors.

This is a continuation of application Ser. No. 941,445 filed Sept. 11,1978, abandoned, which in turn is a division application of Ser. No.797,713, filed May 17, 1977, U.S. Pat. No. 4,127,608.

SUMMARY OF INVENTION

In accordance with this invention, there is provided a method forsynthesizing compounds of the formula: ##STR1## wherein R is ##STR2## or--CH₂ --(CH₂)_(n) --OR₁ ; n is an integer of from 0 to 1 and R₁ takentogether with its attached oxygen atom forms an ester group removable byhydrolysis or an ether group removable by hydrogenolysis or acidcatalyzed cleavage

by condensing a compound of the formula ##STR3## with a compound of theformula: ##STR4## the compound of formula I is converted to Vitamin Ewhich has the following formula: ##STR5##

On the other hand, when R is --CH₂ --(CH₂)_(n) --OR₁, the compound offormula I can be converted to produce the compound of the formula:##STR6## wherein n is as above which are all well-known intermediates inthe synthesis of Vitamin E [see Mayer et al. Helv. Chem. Acta., 46, 650(1963) and Scott et al., Helv. Chem Acta, 59, 290 (1976)].

DETAILED DESCRIPTION

As used throughout this application, the term "lower alkyl" comprehendsboth straight and branched chain saturated hydrocarbon groups containingfrom 1 to 7 carbon atoms such as methyl, ethyl, propyl, isopropyl, etc.As used throughout this application, the term "halogen" includes allfour halogens, such as bromine, chlorine, fluorine and iodine. The term"alkali metal" includes sodium, potassium, lithium, etc.

The term "lower alkoxy" as used throughout the specfication denoteslower alkoxy groups containing from 1 to 7 carbon atoms such as methoxy,ethoxy, propoxy, isopropoxy, etc. The term "lower alkanoyl" as usedthroughout this specification denotes lower alkanoyl groups containingfrom 2 to 6 carbon atoms such as acetyl or propionyl. As used herein theterm "aryl" designates mononuclear aromatic hydrocarbon groups such asphenyl, which can be unsubstituted or substituted in one or morepositions with a lower alkylenedioxy, a halogen, a nitro, a lower alkylor a lower alkoxy substituent, and polynuclear aryl groups such asnaphthyl, anthryl, phenanthryl, azulyl, etc., which can be unsubstitutedor substituted with one or more of the aforementioned groups. Thepreferred aryl groups are the unsubstituted mononuclear aryl groups,particularly phenyl. The term "aryl lower alkyl" comprehends groupswherein aryl and lower alkyl are as defined above, particularly benzyl.The term "aroic acid" comprehends acids wherein the aryl group isdefined as above. The preferred aroic acid is benzoic acid.

As used herein the term "alcohol protecting group" comprehends anyconventional organic alcohol protecting group such as those listed inMcOmie, "Protective Groups in Organic Chemistry," Chapter 3, PlenumPress, New York, 1973; Harrison and Harrison, "Compendium of OrganicSynthetic Methods," Vols. I, II, Sect. 45-A, John Wiley and Sons, NewYork, 1971 and 1974; "Annual Reports in Organic Synthesis", 1970-1975,Sect. V-A, Academic Press, New York, 1971-1976.

Exemplary protecting groups are esters removable by hydrolysis such asacetates, benzoates, trihaloacetates, methanesulfonates andp-toluenesulfonates; ethers removable by hydrolysis such astetrahydropyranyl, t-butyl, methoxymethyl, 2-ethoxyethyl; trialkylsilylethers such as trimethylsilyl and t-butyldimethylsilyl; ethers removableby hydrogenolysis such as benzyl, alkyl or benzhydryl ethers.

The preferred ethers which are removed by acid hydrolysis aretetrahydropyranyl, 2-ethoxyethyl and t-butyl.

The preferred ethers which are removed by hydrogenolysis are benzyl andsubstituted benzyl.

The preferred esters which are removed by acid or base hydrolysis areacetates, formates and benzoates.

In accordance with this invention, the compound of formula III isprepared by reacting a compound of the formula ##STR7## wherein R is asabove with a conventional methylenation agent such as dimethylsulfoniummethylide or dimethyloxosulfonium methylide as disclosed by Corey et al.in J. Amer. Chem. Soc., 84, 3782 (1962); Ibid., 87, 1353 (1965), Ibid.,84, 867 (1962).

In accordance with a preferred embodiment of this invention, thesulfonium methylide is formed by treating trimethylsulfonium chloridewith sodamide in liquid ammonia. After formation of dimethylsulfoniummethylide, the compound of formula X is added to the same reactionmixture in which the dimethylsulfonium methylide was formed.Temperatures are utilized in this reaction to maintain the ammonia in aliquid state during the reaction.

Alternatively, the compound of formula X may be converted to thecompound of formula III by a two-step procedure in which the compound offormula X is first treated with a methylenetriarylphosphorane such asmethylenetriphenylphosphorane to form an olefin of the formula: ##STR8##wherein R is as above.

The methylenetriphenylphosphorane is generated by any conventional meansfor example as disclosed by Wittig et al. in Org. Syn., 40, 66 (1960).For example, it is generated by treatment of amethyltriphenylphosphonium halide, e.g. methyltriphenylphosphoniumbromide with a strong base, such as n-butyllithium in an inert organicsolvent such as tetrahydrofuran. The methylenetriphenylphosphorane isthen reacted with the compound of formula X in the same reaction mixturein which the methylenetriphenylphosphorane was formed.

The compound of formula XI is converted to the compound of formula IIIby oxidation with a peracid. Any conventional peracid may be used suchas peracetic acid, m-chloroperbenzoic acid, monoperphthalic acid andpercamphoric acid. This reaction is carried out by adding a solution ofthe peracid to a solution of the compound of formula XI in an inertorganic solvent such as dichloromethane or acetic acid at a temperatureof -10° C. to room temperature.

When R, in the compound of formula XI is --CH₂ --(CH₂)_(n) --OR₁ and R₁is hydrogen i.e., a compound of the formula: ##STR9## it may beconverted to the compound of the formula III where R is --CH₂--(CH₂)_(n) --OR₁ and R₁ is hydrogen, i.e. a compound of the formula:##STR10## by the above peracid reagents or by epoxidation using anorganic hydroperoxide in the presence of vanadium or molybdenum catalystaccording to the procedure of Sharpless et al., J. Amer. Chem. Soc., 95,6136 (1973); Ibid., 96, 5354 (1974).

In order to form the compound of formula I, the dianion of the compoundof formula II which has the formula: ##STR11## wherein M₁ ⁺ and M₂ ⁺ arealkali metal ions is condensed with the compound of formula III. Thisreaction is carried out in an anhydrous aprotric solvent. Anyconventional anhydrous aprotic solvent can be utilized to carry out thiscondensation. Among the preferred aprotic solvents are included diethylether, tetrahydrofuran, hexamethylphosphoramide, etc. This condensationis carried out at a temperature of from -10° C. to 50° C.

The dianion of formula II-A is prepared from the compound of formula IIvia the monoanion of the formula ##STR12## wherein M₁ is as above.

The compound of formula II is converted to the monoanion of formula II-Bby treating at a temperature of -70° C. to 20° C. the compound offormula II with a base to form the monoanion of formula II-B. In formingthe monoanion, it is preferred to react the compound of formula II withone equivalent of the base per equivalent of the compound of formula II.The preferred bases are sodium hydride, sodamide, lithium dialkylamides,potassium hydride, alkali metal hydroxides or alkoxides or an alkalimetal. The reaction may be carried out in an inert solvent. Among thepreferred solvents are alkanols such as ethanol, methanol, etc., water,diethyl ether, tetrahydrofuran, dimethylformamide orhexamethylphosphoramide. If a solvent other than an aprotic solvent isutilized, it must be replaced by an aprotic anhydrous solvent in orderto carry out the next step of converting the monanion of formula II-B tothe dianion of formula II-A. This non-aprotic solvent can be removed byevaporation to obtain the monoanion, there is added an aprotic anhydroussolvent medium to carry out the conversion of a compound of formula II-Bto the dianion of formula II-A.

The conversion of the monoanion of formula II-B to the dianion offormula II-A is carried out by treating the monoanion of formula II-Bwith a strong base in an anhydrous aprotic solvent at a temperature offrom -70° C. to 20° C. Any conventional solvent can be utilized incarrying out this reaction. Among the strong bases which are suitablefor carrying out this reaction are included alkyl lithium, alkali metaldialkylamides or sodamide. Among the preferred strong bases are includedbutyllithium, methyllithium, lithium diisopropylamide. The formation ofthe dianion of formula II-A is expediently carried out by reacting themonoanion of formula II-B with one equivalent of base per equivalent ofmonoanion. The dianion of formula II-B can be isolated, if desired, bylow temperature evaporation of the solvent. However, since the reactionmedium in which the dianion is formed can be utilized to react thisdianion in the next step with the compound of formula III to form thecompound of formula I, there is no necessity to isolate the dianion offormula II-A.

A preferred method for forming the dianion of the compound of formulaIII is by utilizing the procedure of Weiler, J. Amer. Chem. Soc., 92,6702 (1970) through treatment of the compound of formula III with oneequivalent of sodium hydride in tetrahydrofuran at 0° C. and then withone equivalent of butyllithium at 0° C. in the same solvent.

The compound of formula I is next converted to a compound of the formula##STR13## wherein R is as above and R₁₀ is lower alkyl.

The compound of formula I is converted to the compound of formula XV byreacting the compound of formula I with a di(loweralkyl)acetone-1,3-dicarboxylate such as dimethylacetone-1,3-dicarboxylate in the presence of an alkali metal loweralkoxide in a lower alkanol solvent. Any conventional lower alkanolsolvent such as methanol, ethanol, isopropanol, etc., can be utilized.Alternatively, the reaction may be carried out with an alkali metal saltof the di(lower alkyl)acetone-1,3-dicarboxylate in an inert organicsolvent such as benzene, tetrahydrofuran, diethyl ether, ordimethylformamide. In carrying out these reactions, temperature andpressure are not critical and this reaction can be carried out at roomtemperature and atmospheric pressure. If desired, higher or lowerpressures and/or temperatures can be utilized.

The compound of formula XV is next converted to a compound of theformula ##STR14## wherein R is as above by treatment with an aluminumhydride reducing agent.

The compound of formula XV is converted to the compound of formula XVIby treating the compound of formula XV with an aluminum hydride reducingagent at a temperature of from 120° C. to 180° C. In carrying out thisreaction, any conventional aluminum hydride reducing agent, which doesnot decompose at temperatures above 120° C., preferably from 120° C. to180° C., can be utilized to carry out this reaction. Among the preferredaluminum hydride reducing agents are sodiumdihydrobis[2-methoxyethoxy]aluminate and di(lower alkyl) aluminumhydrides such as diisobutyl aluminum hydride. In carrying out thisreaction, any inert organic solvent can be utilized. Among the preferredinert organic solvents are the inert organic solvents boiling above 120°C. at atmospheric pressure such as diglyme, xylene, etc. If desired,inert organic solvents which are lower boiling can be utilized attemperatures of 120°-180° C., if the reaction is carried out underpressure.

In the next step of this process, the compound of formula XVI isconverted to a compound of the formula: ##STR15## where R is as above byreacting the compound of formula XVI with an oxidizing agent describedhereinafter.

Where R in the compound of formula XV is --CH₂ --(CH₂)_(n) --OR₁, acompound of the formula: ##STR16## wherein n and R₁ are as above isformed which is thereafter converted to a compound of the formula:##STR17## wherein R₁ and n are as above by reacting the compound offormula XVI-A with an oxidizing agent as described hereinafter.

The compound of formula XVI-A is converted to the compound of formulaXVII-A by oxidation with a nitrosodisulfonate salt of the formula##STR18## wherein M is an alkali metal.

Among the preferred nitrosodisulfonate salts are included Fremy's salt.In carrying out this reaction, any of the conditions conventional inoxidizing with Fremy's salt as well as other nitrosodisulfonates can beutilized. Generally, this reaction is carried out in an aqueous medium.In carrying out this oxidation, temperature and pressure are notcritical and this reaction can be carried out at room temperature andatmospheric pressure. On the other hand, elevated or reducedtemperatures can be utilized.

On the other hand, where R in the compound of formula XVI is, ##STR19##i.e., a compound of the formula ##STR20## There is no reaction betweenthe oxidizing agent of formula XX and the compound of formula ##STR21##is not formed.

In accordance with this invention, we have discovered a neworganic-soluble oxidizing agent which will convert the compound offormula XVI-B to the compound of formula XVII-B. This oxidizing agenthas the formula ##STR22## wherein R₁₁, R₁₂ and R₁₃ are alkyl containingfrom 1 to 20 carbon atoms and R₁₄ is alkyl containing 8 to 20 carbonatoms.

The oxidizing agent of formula XXI can also oxidize the compound offormula XVI-A to the compound of formula XVII-A and is generallyeffective in oxidizing phenols usually oxidized with Fremy's salt, e.g.,durophenol.

In the compound of formula XXI, R₁₁, R₁₂ and R₁₃ can be any straight orbranched chain alkyl group containing from 1 to 20 carbon atoms such asmethyl, n-octyl, isopropyl, ethyl, n-decyl 2,4,6-trimethyldodecyl,n-octadecyl, etc. Also, R₁₄ can be any straight or branched chain alkylgroup containing from 8 to 20 carbon atoms such as n-decyl, n-octyl,2,4,6-trimethyldodecyl, n-octadecyl, etc. Among the preferred compoundsof formula XXI are compounds such as tri(n-octyl)mono methyl ammoniumnitrosodisulfonate and tri(n-decyl)mono methylammoniumnitrosodisulfonate.

The compound of formula XXI is formed by reacting the compound offormula XX with a quaternary ammonium salt of the formula ##STR23##wherein R₁₁, R₁₂, R₁₃ and R₁₄ are as above and Y.sup.⊖ is a halide orHSO₄.sup.⊖ ion.

This reaction is carried out in a two phase system consisting of anaqueous solution or suspension of the salt of formula XX and an inertorganic solvent such as toluene, benzene, xylene, etc. In carrying outthis reaction, temperature and pressure are not critical and thisreaction can be carried out at room temperature or atmospheric pressure.The compound of formula XXI is formed in the organic layer. On the otherhand, higher or lower temperatures can be utilized. Generally, thisreaction is carried out at a temperature of from 0° C. to 50° C. Thesalt of formula XXI can be isolated from the reaction medium byseparating the aqueous layer and evaporating the organic solvent.However, since the salt of formula XXI can be utilized to oxidize thecompound of formula XVI to a compound of formula XVII in the solventmedium, one need not isolate the salt of formula XXI from the reactionmedium but may oxidize the compound of formula XVI to the compound offormula XVII directly in the solvent medium.

In addition, the compound of formula XXI need not be formed instoichiometric amount to the phenol of formula XVI-B since the oxidationmay be run by adding a catalytic amount of the quaternary ammonium saltof formula XXII to a two-phase water-organic solvent medium containing astoichiometric amount of the compound of the formula XX. The oxidationcan be run with 0.01-5.0 equivalents of the ammonium salt of formulaXXII.

In carrying out this oxidation reaction, temperature and pressure arenot critical and this reaction can be carried out at room temperatureand atmospheric pressure. On the other hand, elevated or reducedtemperatures can be utilized. Generally, it is preferred to utilizetemperatures of from 0° C. to 50° C.

The compound of formula XVII-B can be converted to Vitamin E by reactionwith sulfuric acid in methanol such as described by Mayer et al. Helv.Chim. Acta, 50, 1168 (1967) or reductive cyclization with butylmercaptan such as disclosed by Oxman and Cohen, Biochem. Biophys. Acta,173, 412 (1966). In the same manner, the compound of formula XVII-A canbe converted to a compound of the formula: ##STR24## wherein R₁ is asabove. Where R₁ forms an ester, any conventional method of esterhydrolysis can be utilized to convert the compound of formula V-A to acompound of formula V. Wherein R₁ forms an ether group removable byhydrogenolysis, any conventional method of hydrogenolysis can beutilized to effect this conversion. On the other hand, where R₁ forms anether group removable by acid catalyzed cleavage, any conventionalmethod of acid catalyzed cleavage can be utilized to effect thisconversion.

The following examples are illustrative but not limitative of theinvention. In the examples, all temperatures are in degrees centigrade.The ether utilized in the following examples is diethyl ether.

EXAMPLE 1 1,2-Epoxy-2,6,10,14-tetramethylpentadecane

To a solution of sodamide in 120 ml of liquid ammonia under reflux(prepared from 9.12 g (0.40 mol) of sodium) was added a solution of 80.0g (0.29 mol) of hexadhydrofarnesylacetone in 300 ml of diethyl etherwhile maintaining a temperature of -33° with external cooling in a DryIce-isopropanol bath. After 15 min 45 g (0.37 mol) of trimethylsulfoniumchloride was added rapidly. After the addition, the Dry Ice condenserwas removed and the ammonia was allowed to evaporate while stirringovernight. The mixture was then cooled in an ice bath and 16.2 g ofammonium chloride was added. The mixture was stirred 30 min at roomtemperature, was filtered through Celite and washed twice with water.The ether solution was washed with brine, was dried over anhydrousmagnesium sulfate and was concentrated on a rotary evaporator to give82.18 g of crude epoxide as an oil. The crude oil (80.93 g) wasdistilled rapidly through a short-path distillation head to give 75.5 gof 1,2-epoxy-2,6,10,14-tetramethylpentadecane, bp 0.08 mmHg=108°-110°.

EXAMPLE 2 7-Hydroxy-7,11,15,19-tetramethyleicosane-2,4-dione

To a suspension of sodium hydride (30.0 g of 57% by weight dispersion,0.72 mol, washed free of oil) in tetrahydrofuran (500 ml) at 0° wasadded dropwise over 30 min a solution of 2,4-pentanedione (71 g, 0.71mol) in 150 ml of tetrahydrofuran to form the monosodium salt of2,4-pentanedione in tetrahydrofuran. After stirring the tetrahydrofuransolution containing the salt for 20 min. at 0°, butyllithium (260 ml of2.5 M solution in hexane, 0.65 mol) was added over 30 min at 0°-5° toform the sodiolithium salt of 2,4-pentanedione and the solutioncontaining this sodiolithium salt was stirred 20 min. at 0°-5°. The1,2-epoxy-2,6,10,14-tetramethylpentadecane (40 g, 0.142 mol) in 50 molof tetrahydrofuran was then added in one portion and the solution wasstirred for 17.5 hr. at room temperature. The solution was cooled to 0°and was poured into a vigorously stirred mixture of ice (2 kg) and conc.aqueous hydrochloric acid (114 ml). Then saturated aqueous ammoniumchloride solution (100 ml) was added and the mixture was extracted withdiethyl ether (3×750 ml). The combined extracts were washed with waterand brine and were dried over anhydrous magnesium sulfate andconcentrated on a rotary evaporator and then at 30°-35°/0.3 mmHg for 2.5hr to give 73.50 g of crude hydroxydiketone7-hydroxy-7,11,15,19-tetramethyleicosane-2,4-dione as an oil. An 0.360 gsample was purified by preparative thin layer chromatograph to give 0.20g of 7-hydroxy-7,11,15,19-tetramethyleicosane-2,4-dione as a lightyellow oil.

EXAMPLE 3 Dimethyl2-hydroxy-4-methyl-6-(3-hydroxy-3,7,11,15-tetramethylhexadecanyl)-benzene-1,3-dicarboxylate

To a solution of 7-hydroxy-7,11,15,19-tetramethyleicosane-2,4-dione(72.5 g) and dimethyl acetonedicarboxylate (29.6 g) in methanol (190 ml)at 0° was added a solution of sodium methoxide in methanol (from 2.44 gof sodium and 90 ml of methanol). The solution was stirred at roomtemperature for 44 hr and was concentrated on a rotary evaporator toremove approx. 100 ml of methanol. The residual solution was poured ontoice (500 g) and 20% (v/v) aqueous hydrochloric acid (45 ml). The mixturewas extracted with ether (3×300 ml) and the combined extracts werewashed with brine and dried over anhydrous sodium sulfate and wereconcentrated on a rotary evaporator to give 91.65 g of crude dimethyl2-hydroxy-4-methyl-6-(3-hydroxy-3,7,11,15-tetramethyl-hexadecanyl)-benzene-1,3-dicarboxylateas an orange oil. A 90.2 g portion of the oil was dissolved in ether(400 ml) and was washed with 20% by weight aqueous potassium carbonate(to remove the unreacted dimethyl acetonedicarboxylate), brine and wasdried over anhydrous sodium sulfate. The solution was concentrated on arotary evaporator to give 83.13 g of partially purified diester dimethyl2-hydroxy-4-methyl-6-(3-hydroxy-3,7,11,15-tetramethyl-hexadecanyl)-benzene-1,3-dicarboxylate.The total material was chromatographed on 2.45 kg of silica gel elutingwith 20-30% by volume ether in hexane to give 30.83 g of dimethyl2-hydroxy-4-methyl-6-(3-hydroxy-3,7,11,15-tetramethyl-hexadecanyl)-benzene-1,3-dicarboxylateas a colorless oil.

EXAMPLE 42,3,6-Trimethyl-5-(3-hydroxy-3,7,11,15-tetramethylhexadecanyl)-phenol

To a solution of the dimethyl2-hydroxy-4-methyl-6-(3-hydroxy-3,7,11,15-tetramethyl-hexadecanyl)-benzene-1,3-dicarboxylate(5.17 g) in xylene (25 ml) at 10° was added sodiumdihydrobis(2-methoxyethoxy)aluminate (20 ml of a 70% by weight solutionin benzene) over 20 min with occasional cooling to keep the temperatureat 10°. After 10 min the solution was heated to reflux for 1.5 hr,cooled to 10° and was poured cautiously into cold 20% by weight aqueoussulfuric acid (200 ml). The mixture was extracted with ether (3×100 ml)and the combined extracts were washed with aqueous sodium bicarbonateand brine and dried (Na₂ SO₄) and concentrated on a rotary evaporator togive 4.29 g of crude2,3,6-trimethyl-5-(3-hydroxy-3,7,11,15-tetramethylhexadecanyl)-phenol asa light yellow oil. Chromatography on silica gel eluting with ether inpetroleum ether gave 3.19 g of pure2,3,6-trimethyl-5-(3-hydroxy-3,7,11,15-tetramethylhexadecanyl)-phenol.

EXAMPLE 5

To a slurry of Fremy's salt (di-potassium nitrosodisulfonate) in sodiumcarbonate (1.6 g) was added 10 ml of 15% sodium carbonate solution and asolution of 0.29 g (0.72 mmol) of tri(caprylyl)monomethylammoniumchloride¹ in 4 ml of benzene. The phenol, i.e.,2,3,6-trimethyl-5-(3-hydroxy-3,7,11,15-tetramethyl-hexadecanyl)-phenol(0.3 g, 0.69 mmol) in 8 ml of benzene was added and the mixture wasstirred vigorously for 2.5 hr. The mixture was poured into 5 ml of waterand was extracted with 10 ml of petroleum ether. The organic phase waswashed with water (2×10 ml) and the cloudy mixture was dried (Na₂ SO₄)and concentrated on a rotary evaporator. The residual crude quinone waschromatographed on 7.0 silica gel eluting with ether-petroleum ether togive 0.321 g tocopheroquinone.

EXAMPLE 6

A solution of Fremy's salt was prepared by dissolving 8.45 g of thesodium carbonate slurry in 52 ml of 15% sodium carbonate followed byadding 0.5 g solid sodium carbonate. The concentration of the solutionwas determined to be 0.175 M by measuring the absorption spectrum at 440nm where ε=14.5. The solution of the Fremy's salt, the phenol, i.e,2,3,6-trimethyl-5-(3-hydroxy-3,7,11,15-tetramethylhexadecanyl)-phenol,tri(capryl)monomethylammonium chloride, and benzene (2 ml) were added inthe amounts given in the table below with the reaction being monitoredby thin layer chromatography to completion. This reaction gavetocopheroquinone.

    __________________________________________________________________________        ON(SO.sub.3 K).sub.2,                                                                    phenol, (C.sub.10 H.sub.21).sub.3 NCH.sub.3 Cl,                Expt.                                                                             ml     (mmol)                                                                            g   (mmol)                                                                            g         (mmol)                                                                             time to completion                      __________________________________________________________________________    1   3.07   (0.537)                                                                           0.1 (0.23)                                                                            0.02       (0.047)                                                                            5 hr.                                  2   3.07   (0.537)                                                                           0.1 (0.23)                                                                            0.09      (0.23)                                                                             2-3 hr.                                 3   3.07   (0.537)                                                                           0.1 (0.23)                                                                            0.18      (0.47)                                                                             20 min.                                 4   3.07   (0.537)                                                                           0.1 (0.23)                                                                            0.37      (0.92)                                                                             20 min.                                 __________________________________________________________________________

EXAMPLE 7

Ten ml of a deep purple 0.154 M solution of Fremy's salt in 5% (w/v)aqueous sodium carbonate was extracted with a solution prepared from1.25 g of tri(n-decyl)monomethylammonium chloride and 10.0 ml ofbenzene. The purple color rapidly was transferred to the benzene layerwhich was separated and dried over anhydrous potassium carbonate to givea benzene solution ofbis[tri(n-decyl)monomethylammonium]nitrosodisulfonate. The solutiondisplayed an absorption maximum in the visible spectrum at λ_(max)=552-8 nm (ε˜15).

When chloroform was used in the extraction in place of benzene, thebis[tri(n-decyl)monoethylammonium]nitrosodisulfonate was obtained in thechloroform layer and after separation and drying displayed infraredabsorptions at λ_(max) =1270 and 1026 cm⁻¹.

EXAMPLE 8

The benzene solution ofbis[tri(n-decyl)monomethylammonium]nitrosodisulfonate prepared inExample 7 was used to oxidize2,3,6-trimethyl-5-(3-hydroxy-3,7,11,15-tetramethylhexa-decanyl)-phenolto tocopheroquinone.

We claim:
 1. A process for producing a compound of the formula ##STR25##wherein R is ##STR26## comprising oxidizing a compound of the formula##STR27## wherein R is as above in the presence of a salt of theformula: ##STR28## in an inert organic solvent medium wherein R₁₁, R₁₂and R₁₃ are alkyl containing from 1 to 20 carbon atoms and R₁₄ is alkylcontaining from 8 to 20 carbon atoms.
 2. The process of claim 1 whereinsaid salt is bis[tri(n-decyl)monomethyl ammonium]nitrosodisulfonate. 3.The process for producing a compound of the formula ##STR29## wherein Ris ##STR30## comprising oxidizing a compound of the formula ##STR31##wherein R is as above with a compound of the formula: ##STR32## whereinM is an alkali metal; in the presence of 0.01-5.0 equivalents of aquaternary ammonium salt of the formula: ##STR33## wherein R₁₁, R₁₂ andR₁₃ are alkyl containing from 1 to 20 carbon atoms and R₁₄ is alkylcontaining from 8 to 20 carbon atoms and Y is halogenin a two phaseaqueous-organic solvent medium.
 4. The process of claim 3 wherein saidquaternary ammonium salt is tri(n-decyl)monomethyl ammonium chloride.